Early recognition and treatment of Transient Ischaemic Attack (TIA)

1. Early recognition and treatment of Transient Ischaemic Attack (TIA) Prof. Pierre Amarenco, Paris, France

2. What is a TIA…. • “Brief episode of neurologic dysfunction caused by focal brain or retinal ischemia, with clinical symptoms typically lasting less than one-hour • and without evidence of acute infarction”. Albers GW, Caplan LR, Easton JD et al. N Engl J Med 2002;347:1713-16

3. TIA : Symptom of stroke or ministroke ?

4. Four Different Perspectives to define « TIAs » • In the community: Recognition of transient symptoms to detect patients at risk for imminent stroke: • Transient Neurologic Symptoms or • Acute CerebroVascular Syndrome • Epidemiology study: differentiiation between transient and permanent symptoms without necessary brain imaging available (duration might be useful) • Therapeutic trials: differentiation between TIA without brain lesion from those with brain lesion (qualifying for brain infarction) • In the setting of a stroke unit: differentiation between transient symptoms from persisting symptoms eligible for tPA, and later between transient symptoms with brain lesion (infartion) and those without (e.g, different prognosis, risk stratification perspective)

5. Four Different Perspectives to define « TIAs » • In the community: Recognition of transient symptoms to detect patients at risk for imminent stroke: • Transient Neurologic Symptoms or • Acute CerebroVascular Syndrome • Epidemiologic study: differentiiation between transient and permanent symptoms without necessary brain imaging available (duration might be useful) • Therapeutic trials: differentiation between TIA without brain lesion from those with brain lesion (qualifying for brain infarction) • In the setting of a stroke unit: differentiation between transient symptoms from persisting symptoms eligible for tPA, and later between transient symptoms with brain lesion (infartion) and those without (e.g, different prognosis, risk stratification perspective)

6. Four Different Perspectives to define « TIAs » • In the community: Recognition of transient symptoms to detect patients at risk for imminent stroke: • Transient Neurologic Symptoms or • Acute CerebroVascular Syndrome • Epidemiology study: differentiiation between transient and permanent symptoms without necessary brain imaging available (duration might be useful) • Therapeutic trials: differentiation between TIA without brain lesion from those with brain lesion (qualifying the neurologic event as a brain infarction) • In the setting of a stroke unit: differentiation between transient symptoms from persisting symptoms eligible for tPA, and later between transient symptoms with brain lesion (infartion) and those without (e.g, different prognosis, risk stratification perspective)

7. Four Different Perspectives to define « TIAs » • In the community: Recognition of transient symptoms to detect patients at risk for imminent stroke: • Transient Neurologic Symptoms or • Acute CerebroVascular Syndrome • Epidemiology study: differentiiation between transient and permanent symptoms without necessary brain imaging available (duration might be useful) • Therapeutic trials: differentiation between TIA without brain lesion from those with brain lesion (qualifying for brain infarction) • In the setting of a stroke unit: differentiation between transient symptoms from persisting symptoms eligible for tPA, and later between transient symptoms with brain lesion (infartion) and those without (e.g, different prognosis, risk stratification perspective)

8. Current view • Use the term • “Cerebrovascular syndrome” to qualify any suspiscion of ischemic stroke (whether transient or permanent, ischemic or hemorrhagic) • Keep the term • “TIA” for symptoms without brain lesion on neuro-imaging

9. 25 OXVASC 14 20 12 OCSP 10 15 8 Risk of stroke (%) 6 10 4 TIA 5 2 Minor stroke 0 0 0 7 14 21 28 0 30 60 90 Days Days Cumulative risk of stroke TIA vs minor stroke Cumulative risk of stroke after TIA BMJ 2004; 328: 326-8 Lancet 2005; 366: 29-36

10. TIA: diagnosis needed • 2,416 pts [OXVASC, OCSP, ECST, UK-TIA] • 23% of strokes preceded by a TIA • 17% same day • 9% day before • 43% within 7 days before index stroke Rothwell P et al. Neurology 2005;64:817-820

11. Very Early Management in a TIA Clinic : 80% stroke risk reduction at 3 months EXPRESS Next day visit SOS-TIA Same day visit (24/24hr) Lavallée et al. Lancet Neurol. 2007 Rothwell et al. Lancet. 2007

12. SOS-TIA • TIA clinic, 24/24 h, 7/7 d • Objectives : • To make an urgent diagnosis of TIA • To find out the cause in less than 4 hours • To prevent a stroke within the next hours/days/weeks

13. Educational leaflet on TIA Mailed to: 15 000 PCP, cardiologists, ophthalmologists, emergency physicians, neurologists in Ile-de-France (administrative region of Paris)

14. Yesterday, I was watching TV, and suddendly the Remote control fell down from my right hand. I could not move my fingers during 3 minutes. And then, suddendly I have totally recovered. Is it some fatigue, Doctor? Do you know? This is a TIA This patient is at risk for a massive stroke within the next hours? Give 300 mg of ASA Pre-hospital What to do? Don’t down grade the symptoms Tell the patient he is at risk for imminent stroke but that we can avoid it Tell him we have to do immediate diagnostic testing and treatment

15. TIA symptoms: Carotid (anterior circulation) • transient monocular blindness • hemiplegie • hemi sensory loss • speech difficulties (aphasia) Vertebrobasilar (posterior circulation): • hemiplegie (may involved both sides, not at the same moment) • unilateral paresthesia (same) • total or partial visual field defect (one or both sides) • ataxia with gait unstability

17. SUSPICION of TIA SOS TIA N°Vert 0 800 888 248 24/24 - 7/7 Nurse practitioner : Monday - Friday 9h to 17 h Senior Vascular Neurologist on duty 17h to 9h and w.e. TIA POSSIBLE ADMISSION at the Day Clinic

18. Lavallée et al. Lancet Neurol. 2007 SOS-TIA 100% of patients had their work-up done in < 4 hrs 75% of patients were discharged home 3 or 4 hrs after admission to the SOS-TIA clinic 2003-2005

19. LOS 1st Step Recognition of TIAs - PCPs GPs - Cardiologists - Ophthalmologists 100% 100% ABCD2 score 2nd Step Admission to TIA Clinic Admission To Stroke Unit Vs. 25% 3rd Step Admission to Stroke Unit 100% 75% 6.5 days Discharge SOS-TIA Model vs. Usual Care TRIAGE Stratifying the risk According to a quick work-up And underlying cause < 1 day vs.

20. European Stroke Organisation 2008 Recommendations Cerebrovasc Dis. 2008;25(5):457-507. Epub 2008 May 6

21. NICE recommendations July 2008

22. ABCD2 Score Johnston C, Rothwell PM etal. Lancet 2006

23. Short-Term Risk of Stroke by ABCD2 Score Johnston C, Rothwell PM etal. Lancet 2006

24. 1622 -> 1176 Definite or possible TIAs

25. 1622 -> 1176 Definite or possible TIAs Does ABCD2 score less than 4 allow more time to evaluate patients with TIA ? Amarenco P, Labreuche J, Lavallée PC, et al. Stroke. 2009

27. SOS-TIA update 2003-2009

28. CLINICAL EVENTS MARKERS OF RISK MODIFIABLE RISK FACTORS Predicting Short/Long-Term High-Risk of Stroke/MI TIA Stroke/MI DWI/MRI Stenosis Plaque Intima-Media Thickness A-Fib Other CSE HTN/Diabetes/Cholesterol/Smoking… Genes / Age / Gender / Hs-CRP / ACE / TM …

29. Triaging TIAs: MRI Calvet D et al. Stroke. 2009;40:187-192

30. 10 9 DWI- imaged cohorts 8 CT- imaged cohorts 7 6 OR for infarction on brain imaging 5 4 3 2 1 0 ≤1 2 3 4 5 6 7 ABCD2 score ABDC2 + I Giles M, Rothwell PM, Amarenco P, et al. Stroke 2010

31. ABDC2 + I Giles M, Rothwell PM, Amarenco P, et al. Stroke 2010

32. Causes of Brain Infarctions Intracranial Atherosclerosis Penetrating Artery Disease CarotidPlaque with Arteriogenic Emboli Flow Reducing Carotid Stenosis Aortic Arch Plaque Atrial Fibrillation Cardiogenic Emboli Valve Disease Left Ventricle Thrombi

33. SOS-TIAUltra-early Neurosonographic evaluation in definite TIA 13% ECG abnormalities (10% AF) Carotid US 97.3% of 1881pts Carotid athero Carotid stenosis ≥70% 65% 8.6% 13.9% 14% 2% 19% DTC 97.3% of 1881 pts Intracranial stenosis Or occlusion Aortic arch pl≥4 mm Major CSE PFO/ASA TTE/TEE 96%/77% of pts Lavallée PC, Labreuche J, Meseguer E et al. & Meseguer E, Lavallée PC, Mazighi M, et al. & Slaoui T, Lavallée PC, Labreuche J et al.

34. SOS-TIA: stratifying the risk with TCD Meseguer E, Lavallée PC, Mazighi M, et al. Ann Neurol. 2010

35. SOS-TIAStratifying the risk on the presence of carotid plaque on carotid ultrasound examination N=1756 Carotid plaque Age and sex adjusted RR=1.83 (95%CI, 0.84-4.01) log-rank, p=0.001 No carotid plaque Risk of combined stroke, myocardial infarction and vascular death from time of presenting with suspected TIA according to presence or absence of ICA atherosclerosis 1-yr rate of Stroke, MI, Vasc Death 3.7% vs. 1.3%

36. SOS-TIA: Immediate Preventive Strategy for Mr B. • Antiplatelet agent, pre-hospital • Blood pressure lowering • Statin therapy (after lipid profile determination in fasting condition) • Smoking cessation • Anti diabetic treatment • Oral anticoagulant (e.g., Atrial fibrillation) • Carotid endarterectomy (stenosis ≥70%)

37. CONCLUSIONS • • TIA is an emergency: work-up has to be done < 24 hours, in a dedicated organized structure (TIA clinic) • With fast evaluation = same day discharged for up to 75% of pts (Pt satisfaction/Cost-effectiveness) • Risk becomes extremely low compared to that expected with a RRR= 80% at 3 months • TIAclinic should be developed in all comprehensive stroke centres for same day evaluation • It is no longer possible to wait more than 12 hours to do the evaluation of a TIA

38. What should be the early management of TIA patients • Admission to a dedicated structure (no matter the setting) • Immediate evaluation and treatment • A priori defined immediate process of care • Brain imaging • Arterial and cardiac evaluation • Blood testing • Full clinical evaluation • Decision on orientation by a senior stroke specialist: discharged home or admission to SU